原发性血小板增多症、真性红细胞增多症和骨髓纤维化：目前的处理和靶向治疗

最近发现JAK2和／或MPL突变对真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）的诊断和治疗产生着重大影响。例如,JAK2突变目前认为是诊断PV的必要条件,WHO分类系统最近修订的PV、ET和PMF诊断标准中包括JAK2和MPL（血小板生成素受体）突变作为克隆性标记。从治疗学的观点,JAK—STAT信号途径现已确定为研发骨髓增殖性新生物治疗新药的合理靶途径。本文简述ET、PV和PMF目前的处理,并复习抗JAK2小分子药物临床前和临床活性的有关资料。     

胃癌合并原发性血小板增多症1例

原发性血小板增多症(essential thrombocythemia,ET)是一种造血干细胞克隆性疾病,引起外周血血小板计数(PLT)明显升高,骨髓中巨核细胞增殖旺盛,约50%~70%的患者有JAK2/V617F基因突变[1],另有一部分患者有MPL及CALR等基因突变。2008年世界卫生组织(WHO)把ET和真性红细胞增多症(PV)、原发性骨髓纤维化(PMF)同时划为BCR-ABL融合基因阴性的骨髓增殖性肿瘤(MPN)。     

骨髓增殖性肿瘤120例JAK2 V617F基因突变的临床分析

目的 探讨JAK2 V617F基因突变在骨髓增殖性肿瘤(MPN)患者中的发生率及临床意义.方法 采用骨髓细胞学和活组织检查方法分析120例患者的骨髓病理状况,监测费城染色体(Ph染色体)和bcr-abl融合基因.从患者骨髓抽提DNA,采用荧光定量PCR技术检测JAK2 V617F基因突变.结果 所有患者均呈现出MPN各自类型的典型特征.Ph染色体和bcr-abl融合基因检测均为阴性.120例MPN患者中JAK2 V617F基因突变的阳性率为66.7％(80/120),其中真性红细胞增多症(PV)为72.7％(16/22),原发性血小板增多症(ET)为66.0％(62/94),4例原发性骨髓纤维化(PMF)患者中2例阳性.JAK2 V617F突变阳性PV患者的外周血白细胞计数(P=0.001)和血小板计数(P=0.010)均高于阴性患者;JAK2 V617F突变阳性ET患者的白细胞计数高于阴性患者(P=0.006);PMF中JAK2V617F突变阳性和阴性患者间各项指标差异均无统计学意义(均P＞0.05).结论 JAK2 V617F基因突变检测有助于bcr-abl阴性MPN的诊断和鉴别诊断,使患者能够在早期被发现和治疗.     

JAK1/2抑制剂治疗骨髓增殖性肿瘤的研究进展

bcr-abl阴性的骨髓增殖性肿瘤(MPN)包括真性红细胞增多症(PV)、原发性血小板增多症(ET)和原发性骨髓纤维化(PMF).随着JAK2 V617F基因突变在MPN患者中的发现,一系列针对该突变的小分子靶向药物被研发,其中通过COMFORT-Ⅰ和COMFORT-Ⅱ等试验研究的JAK1/2抑制剂芦可替尼(ruxolitinib)已经被美国食品和药品管理局(FDA)和欧洲药品管理局(EMA)批准应用于中晚期PMF患者和羟基脲耐药或不耐受PV患者的治疗,给MPN患者带来了新的希望.     

血红蛋白及血小板增多患者的JAK2 V617F突变检测及临床意义分析

骨髓增殖性肿瘤（myeloproliferative neoplasm,MPN）是以一系或多系分化相对成熟的骨髓细胞克隆性增殖异常为特点的疾病,其分类中的真性红细胞增多症（polycythemia vera,PV）、原发性血小板增多症（essentialthrombocythemia,ET）等疾病中存在JAK2V617F点突变。有研究表明,在检测MPN患者JAK2V617F突变中,PV发生率在90％以上、ET发生率为50％-70％。JAK2V617F基因突变已作为诊断MPN的必要指标之一。本研究目的是对血红蛋白及血小板增多临床怀疑MPN者进行JAK2V617F突变检测,并结合临床资料进行分析,为血红蛋白及血小板增高患者的诊断提供依据。     

原发性血小板增多症骨髓病理及JAK2-V617F突变分析

目的:分析原发性血小板增多症（essential thrombocythemia,ET）患者的骨髓病理及JAK2-V617F突变特点。方法:回顾109例ET患者的临床资料,并与继发性血小板增多症(secondary thrombocythemia,ST)进行比较。结果:ET骨髓病理巨核细胞体积明显增大,核多分叶、多核易见,成簇、成片状分布,ST巨核细胞体积未见明显增大及异常分布。ET患者JAK2-V617F突变阳性率为 57.83%,ST患者JAK2-V617F突变均为阴性。JAK2-V617F突变阳性组WBC、Hb、骨髓纤维化、初诊血栓事件高于阴性组,差异有统计学意义（P<0.05)。JAK2-V617F突变阳性组年龄、Plt、骨髓粒系、红系百分比及巨核细胞计数与阴性组比较,无显著性差异（P>0.05）;JAK2-V617F突变阳性组无血栓生存率较阴性组低,差异有统计学意义（P<0.05）。结论:ET的骨髓病理特征明显,骨髓活检与JAK2-V617F基因检查相结合对ET诊断及治疗具有重要意义。     

干扰素α联合亚砷酸治疗JAK2V617F突变阳性真性红细胞增多症和原发性血小板增多症的疗效

目的:观察干扰素α（interferon-α,IFN-α）联合亚砷酸治疗JAK2V617F突变阳性的真性红细胞增多症（polycythemia vera,PV）和原发性血小板增多症（essential thrombocythemia,ET）患者的有效性及安全性。方法:回顾性分析2015年12月至2021年01月在我院血液科收治的44例PV和ET患者的临床资料,比较IFN-α联合亚砷酸（观察组）以及单用IFN-α（对照组）的疗效及不良反应。结果:观察组血液学总有效率（overall response rate,ORR）为88.5%,高于对照组。至随访截止时,观察组达血液学及分子生物学缓解的ORR均高于对照组。并且观察组并未出现不良反应发生率增加的情况。结论:亚砷酸能加速并增强IFN-α抗肿瘤作用,二者联合治疗能提高JAK2V617F突变阳性的PV和ET的临床缓解率和疗效持续时间,且安全性高。     

CALR基因突变的原发性血小板增多症三例并文献复习

目的 探讨原发性血小板增多症(ET)中CALR基因突变患者的临床特征.方法 报道宁夏回族自治区人民医院确诊的3例CALR基因突变的ET患者,并进行相关文献复习.结果 结合实验室、骨髓检查及CALR基因检测结果,3例患者明确诊断为CALR基因突变阳性ET,长期给予阿司匹林联合干扰素α治疗,病情稳定.结论 CALR基因在JAK2和MPL阴性的骨髓增殖性肿瘤患者中具有重要诊断价值.     

骨髓增殖性肿瘤CALR基因突变的研究进展

骨髓增殖性肿瘤(MPN)是一类以一系或多系髓系细胞增殖为主要特征的克隆性造血干细胞疾病,分为bcr-abl融合基因阳性的慢性粒细胞白血病和bcr-abl阴性MPN,后者主要包括真性红细胞增多症(PV)、原发性血小板增多症(ET)和原发性骨髓纤维化(PMF)3种经典类型.随着JAK2、MPL等突变基因的不断发现,对这类疾病的认识有了巨大进展.但JAK2/MPL突变双阴性MPN患者的遗传学基础仍不完全清楚.近年研究发现JAK2/MPL未突变的MPN患者获得新的CALR突变,且该类患者表现出明显不同的临床特征,为疾病诊断和预后评价提供了一个新的分子标准.文章就CALR基因突变的发现及其介导MPN发生的机制研究等作一综述.     

JAK2 V617F基因突变阳性骨髓增殖性肿瘤治疗研究进展

JAK2 V617F基因突变阳性骨髓增殖性肿瘤(MPN)由真性红细胞增多症(PV)、原发性血小板增多症(ET)和原发性骨髓纤维化(PMF)组成.文章聚焦于其危险度积分系统和治疗进展,包括一线及二线治疗、JAK2抑制剂、降细胞治疗、抗纤维化和其他单药或联合治疗.     

Etoposide, dexamethasone, cytarabine, and cisplatin in vincristine, doxorubicin, and dexamethasone-refractory myeloma

Based on remarkable activity in refractory lymphomas, a combination of etoposide, cisplatin (both administered by 4-day continuous infusions), cytarabine (Ara-C), and dexamethasone (EDAP) was evaluated in 20 patients with advanced myeloma refractory to standard melphalan and prednisone (MP) and/or vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and dexamethasone (VAD) and even to high doses of melphalan (HDM) (seven patients). Forty percent of patients responded regardless of previously recognized risk factors (eg, duration of drug resistance, tumor mass, and serum lactic dehydrogenase [LDH] level). While the median survival was only 4.5 months, patients with good performance (Zubrod less than 2) and low or intermediate tumor stage survived more than 14 months compared with only 2 months for the remaining group. EDAP could be readily administered in the outpatient clinic, but neutropenic fever prompted hospital admission in 80% of patients, half of whom developed penumonia and sepsis, a fatal outcome in four patients. Severe myelosuppression was of short duration, so that subsequent cycles could be administered every 3 to 4 weeks. No serious extramedullary toxicity, including renal toxicity, was encountered. Marrow toxicity and hence infectious complications may be reduced by elimination of Ara-C without compromising treatment efficacy. We conclude that the lack of cross-resistance with VAD and even HDM makes EDAP or a similar combination an attractive regiment to be formally explored in an alternating sequence with VAD in high-risk myeloma.     

Premenopausal intakes of vitamins A, C, and E, folate, and carotenoids, and risk of breast cancer.

Intakes of vitamins A, C, and E, folate, and carotenoids have been hypothesized to reduce the risk of breast cancer. However, previous epidemiological studies on these nutrients and breast cancer risk have been inconclusive, and have included primarily postmenopausal women. We examined the intake of these nutrients in relation to breast cancer risk among 90,655 premenopausal women ages 26-46 years in 1991 in the Nurses' Health Study II. Nutrient intake was assessed with a validated food-frequency questionnaire at baseline in 1991 and in 1995. During 8 years of follow-up from 1991 to 1999, we documented 714 incident cases of invasive breast cancer. Overall, none of the vitamins and carotenoids was strongly related to a reduced risk of breast cancer. However, intake of vitamin A, including preformed vitamin A and carotenoids, was associated with a reduced risk of breast cancer among smokers; participants in the highest quintile of total vitamin A intake had a multivariate relative risk of 0.28 (95% confidence interval 0.12-0.62; P, test for trend <0.001; P, test for interaction <0.001) compared with those in the lowest quintile of intake. We found no evidence that higher intakes of vitamins C and E, and folate in early adult life reduce risk of breast cancer. However, intake of vitamin A may be related to a reduced risk of breast cancer among smokers.     

Myelodysplastic syndromes, aging, and age: correlations, common mechanisms, and clinical implications

Myelodysplastic syndromes (MDS) are a heterogenous group of myeloid neoplasms that develop primarily in elderly patients. Although a specific molecular basis for the predominant incidence of MDS in higher age groups remains unknown, several lines of evidence suggest that the biology of aging and the pathogenesis of MDS share several genetic, epigenetic, and molecular features. The current review attempts to delineate these common aspects as well as additional discriminative features that are specific for MDS and thus help explaining disease-evolution and progression. In addition, the present review discusses age as an important prognostic factor and co-variable to be considered in treatment algorithms in MDS.     

Clinical trial discussion, referral, and recruitment: physician, patient, and system factors

Purpose

Patient participation in cancer clinical trials is imperative to the advancement of medical science. Physicians play an important role in recruitment by discussing clinical trials with their cancer patients. Patient–physician discussion is influenced by many factors relating to the physician, the patient, and the healthcare system.

Methods

Physicians selected from the 2008–2009 American Medical Association Physician Masterfile who practiced in California, Florida, Illinois, or New York and specialized in medical oncology, surgery, or radiation oncology were surveyed about their attitudes and practices with respect to breast cancer clinical trials. Practice types were categorized according to the classifications provided by the American College of Surgeons, and clinical trial and practice addresses were geocoded.

Results

Surveys were completed by 706 of 1,534 eligible physicians (46 %). Medical oncologists were more likely than surgical or radiation oncologists to discuss the possibility, benefits, and risks of clinical trial enrollment with their breast cancer patients. Physicians who spent the most time in patient care were least likely to discuss clinical trials with their patients. Distance from a physician’s practice to the nearest clinical trial site was inversely associated with referral and recruitment. Perceived barriers to clinical trial participation were associated with greater referral activity suggesting that physicians who were more involved in trials were also more likely to understand barriers to participation.

Conclusions

Multilevel interventions may be successful at increasing participation of women in clinical trials.